Direct Differentiation of Adult Ocular Progenitors into Striatal Dopaminergic Neurons

Abstract

Parkinson’s disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson’s disease.

Efficient induction of neural precursor cells from fibroblasts using stromal cell-derived inducing activity

“…that stromal cells produce a variety of factors that support neural differentiation without inducing mesodermal markers [24,25] and that the time course of neural marker induction by SDIA is similar to that observed in early neural development [16]. Although the SDIA method has beneficial advantages, it also has the unsolved problem that the stromal cells used are not from animal-free conditions.…”